Acute and 2-week exposure to prednisolone impair different aspects of β-cell function in healthy men

Abstract

Objective: Glucocorticoids (GCs), such as prednisolone, are associated with adverse metabolic effects, including glucose intolerance and diabetes. In contrast to the well known GC-induced insulin resistance, the effects of GCs on β-cell function are less well established. We assessed the acute and short-term effects of prednisolone treatment on β-cell function in healthy men. Research design and methods: A randomised, double-blind, placebo-controlled trial consisting of two protocols was conducted. In protocol 1 (n = 6), placebo and a single dose of 75 mg of prednisolone were administered. In protocol 2 (n = 23), participants received 30 mg of prednisolone daily or placebo for 15 days. Both empirical and model-based parameters of β-cell function were calculated from glucose, insulin and C-peptide concentrations obtained during standardised meal tests before and during prednisolone treatment (protocols 1 and 2), and 1 day after cessation of treatment (protocol 2). Results: Seventy-five milligrams of prednisolone acutely increased the area under the postprandial glucose curve (AUCgluc; P = 0.005), and inhibited several parameters of β-cell function, including AUCc-pep/ AUCgluc ratio (P = 0.004), insulinogenic index (P = 0.007), glucose sensitivity (P = 0.02) and potentiation factor ratio (PFR; PZ0.04). A 15-day treatment with prednisolone increased AUCgluc (P < 0.001), despite augmented C-peptide secretion (P = 0.05). β-cell function parameters were impaired, including the fasting insulin secretory tone (P = 0.02) and PFR (P = 0.007). Conclusions: Acute and short-term exposure to prednisolone impairs different aspects of β-cell function, which contribute to its diabetogenic effects. © 2010 European Society of Endocrinology.